The Hox Gene,abdominal Acontrols timely mitotic entry of neural stem cell and their growth during CNS development inDrosophila

Abstract

AbstractThe size of a cell is important for its function and physiology. Interestingly, size variation can be easily observed in clonally derived embryonic and hematopoietic stem cells. Here, we investigated the regulation of stem cell growth and its association with cell fate. We observed heterogeneous sizes of neuroblasts or neural stem cells (NSCs) in theDrosophilaventral nerve cord (VNC). Specifically, thoracic NSCs were larger than those in the abdominal region of the VNC. Our research uncovered a significant role of the Hox geneabdominal A(abdA) in the regulation of abdominal NSC growth. Developmental expression of AbdA retards their growth and delays mitotic entry compared to thoracic NSCs. The targeted loss ofabdAenhanced their growth and caused an earlier entry into mitosis with a faster cycling rate. Furthermore, ectopic expression ofabdAreduced the size of thoracic NSCs and delayed their entry into mitosis. We suggest thatabdAplays an instructive role in regulating NSC size and exit from quiescence. This study demonstrates for the first time the involvement ofabdAin NSC fate determination by regulating their growth, entry into mitosis and proliferation rate, and thus their potential to make appropriate number of progeny for CNS patterning.Significance statementUnderstanding the upstream regulation of various aspects of the cell cycle is very important, how cell growth influences the process is largely unknown.We found an instructive role of the Hox geneabdominal Ain maintaining the small size of neural stem cells (NSCs) and limiting their ability to undergo mitosis.This mechanism is crucial, as it helps NSCs generate the necessary number of neurons at the appropriate developmental stage, thereby contributing to proper central nervous system patterning.